Metal–carbene-guided twofold cross-coupling of ethers with chromium catalysis

Abstract

Coupling by metal–carbene transfer enables the formation of several different bonds at the carbenoid site, enabling prochiral Csp3 centers that are fundamental three-dimensional substructures for medicines to be forged with increased efficiency. However, strategies using bulk chemicals are rare because of the challenge of breaking two unactivated geminal bonds. Herein, we report the reactivity of ethers to form metal–carbene intermediate by cleavage of α-Csp3–H/Csp3–O bonds, which achieve selective coupling with arylmagnesium bromides and chlorosilanes. These couplings are catalysed by cyclic (alkyl)(amino)carbene-chromium complex and enable the one-step formation of 1,n-arylsilyl alcohols and α-arylated silanes. Mechanistic studies indicate that the in-situ formed low-valent Cr might react with iodobenzene to form phenyl radical species, which abstracts the α-H atom of ether in giving α-oxy radical. The latter combines with Cr by breaking α-Csp3–O bond to afford metal–carbene intermediate, which couples with aryl Grignard and chlorosilane to form two σ-bonds. Harnessing carbenoid intermediates during organic transformations is an essential strategy for catalysis but strategies using bulk chemicals are rare due to the challenge of breaking two unactivated geminal bonds. Here, the authors report the reactivity of readily available ethers to form a metal–carbene intermediate via radical-relay bond cleavage.